High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Long-term infection of schistosomiasis will seriously affect the liver health of patients. The serum of 334 chronic Schistosoma japonicum patients and 149 healthy volunteers was collected. Compared with heathy people, the level of C4 (complement 4) was increased, and the level of C3 (complement 3) was in an obvious skewed distribution. ELISA was performed to detect the serum cytokines, the results showed that the levels of IFN-γ (interferon-γ), IL (interleukin)-2 and TNF-α (tumour necrosis factor-α) were reduced, while the levels of Th2 cytokines (IL-4, IL-6 and IL-10) were increased. In the serum of patients with high C3, the secretion of HA (hyaluronic acid), LN (laminin), IV-C (type IV collagen) and PCIII (type III procollagen) were increased, the activation of hepatic stellate cells was promoted. Exogenous human recombinant C3 made mice liver structure of the mice damaged and collagen deposition. IFN-γ and IFN-γ/IL-4 were decreased, while HA, LN, PCIII and IV-C were increased, and the expressions of α-SMA and TGF-ß1 in liver tissues were up-regulated. However, the addition of IFN-γ partially reversed the effect of C3 on promoting fibrosis. High level of C3 is associated with Th2 immune response and liver fibrosis in patients with schistosomiasis.

Structure-based discovery of potent myosin inhibitors to guide antiparasite drug development.

Monogenea, a prevalent parasite in aquaculture, poses significant threats to the industry, leading to substantial losses. Current preventive measures have proven insufficient, necessitating the development of novel and effective anti-parasitic drugs. In this investigation, we obtained the full-length myosin cDNA sequence by analyzing three-generation transcriptome data, revealing a 5817-base sequence encoding 1938 amino acids. Subsequently, we modeled and analyzed the characteristics of the secondary and tertiary of myosin, pinpointing the crucial functional region within the motor domain (amino acids 1-768). The prokaryotic expression of this domain yielded a protein of 87.44 kDa, confirmed as myosin by Western Blotting. Molecular docking identified ASN439 as the key amino acid residue involved in arctigenin and myosin binding, a result corroborated by site-directed mutagenesis, affirming the active cavity of this interaction. Chalcone and shikonin were chosen from a virtual sieve of molecular library of natural drugs based on the active cavity. Chalcone and shikonin exhibited EC50 values of 1.085 mg/L and 0.371 mg/L, respectively, with corresponding IC50 values for myosin of 0.44 mM and 0.14 mM. Given its superior activity and structure, shikonin was selected for further optimization of drug molecule design, culminating in the discovery of 1,4-naphthoquinone as a potent antiparasitic agent. This compound demonstrated an EC50 of 0.047 mg/L, LC50 of 0.23 mg/L, and a TI index of 4.893. These findings collectively highlight the potential of shikonin and 1,4-naphthoquinone as alternative compounds to control Gyrodactylus infections. Further optimization of medicinal chemistry holds promise for the development of more potent 1,4-naphthoquinone analogues, offering prospects for future anthelmintic control through combinatorial or replacement strategies.

Secondhand smoke exposure can increase the risk of first ischemic stroke: A 10.7-year prospective cohort study in China.

INTRODUCTION: Passive smoking is considered a major public health issue in China. Prospective evidence regarding the link between secondhand smoke (SHS) and ischemic stroke in China is scarce. METHODS: The China Kadoorie Biobank (CKB) study in Liuzhou City recruited 50,174 participants during 2004-2008. Of these 30,456 never-smokers were included in our study. The median follow-up period was 10.7 years. The incidence of ischemic stroke was obtained through the China Disease Surveillance Points (DSP) system and the Health Insurance (HI) database. Cox proportional risk models were used to evaluate the association between SHS exposure and ischemic stroke. RESULTS: During 320,678 person-years of follow-up, there were 2059 patients with ischemic stroke observed and the incidence of ischemic stroke was 6.42 per thousand person-years. Participants exposed to SHS daily faced a 21 % higher risk of ischemic stroke (HR = 1.21, 95 %CI: 1.09-1.34) compared to those exposed to SHS less than once a week. Subgroup analyses revealed that daily SHS exposure was linked to heightened risk of ischemic stroke among women, non-employed, and non-weekly tea drinkers. CONCLUSIONS: Daily SHS exposure was associated with higher risks of ischemic stroke. Proactive tobacco control strategies are necessary to decrease the risk of ischemic stroke in never smokers.

Pneumocephalus and empyema in the subarachnoid space: An unusual imaging feature secondary to spinal-epidural anesthesia.

Pneumocephalus and empyema in the subarachnoid space secondary to spinal-epidural anesthesia are very rare and have not previously been reported, to our knowledge. Here, we describe the imaging features of an older woman presenting with pneumocephalus plus subarachnoid and intraventricular empyema due to Staphylococcus epidermidis infection after spinal-epidural anesthesia, with the aim of raising awareness regarding this serious complication.

Spicy food consumption reduces the risk of ischaemic stroke: a prospective study.

Previous studies revealed that consuming spicy food reduced mortality from CVD and lowered stroke risk. However, no studies reported the relationship between spicy food consumption, stroke types and dose­response. This study aimed to further explore the association between the frequency of spicy food intake and the risk of stroke in a large prospective cohort study. In this study, 50 174 participants aged 30­79 years were recruited. Spicy food consumption data were collected via a baseline survey questionnaire. Outcomes were incidence of any stroke, ischaemic stroke (IS) and haemorrhagic stroke (HS). Multivariable-adjusted Cox proportional hazard models estimated the association between the consumption of spicy food and incident stroke. Restricted cubic spline analysis was used to examine the dose­response relationship. During the median 10·7-year follow-up, 3967 strokes were recorded, including 3494 IS and 516 HS. Compared with those who never/rarely consumed spicy food, those who consumed spicy food monthly, 1­2 d/week and 3­5 d/week had hazard ratio (HR) of 0·914 (95 % CI 0·841, 0·995), 0·869 (95 % CI 0·758, 0·995) and 0·826 (95 % CI 0·714, 0·956) for overall stroke, respectively. For IS, the corresponding HR) were 0·909 (95 % CI 0·832, 0·994), 0·831 (95 % CI 0·718, 0·962) and 0·813 (95 % CI 0·696, 0·951), respectively. This protective effect showed a U-shaped dose­response relationship. For obese participants, consuming spicy food ≥ 3 d/week was negatively associated with the risk of IS. We found the consumption of spicy food was negatively associated with the risk of IS and had a U-shaped dose­response relationship with risk of IS. Individuals who consumed spicy food 3­5 d/week had a significantly lowest risk of IS.

Implications for TB control among migrants in large cities in China: A prospective population-based genomic epidemiology study in Shenzhen.

Internal migrants are a challenge for TB control in large Chinese cities and understanding this epidemiology is crucial for designing effective control and prevention strategies. We conducted a prospective genomic epidemiological study of culture-positive TB patients diagnosed between June 1, 2018 and May 31, 2021 in the Longhua District of Shenzhen. Treatment status was obtained from local and national TB registries and all isolates were sequenced. Genomic clusters were defined as strains differing by ≤12 SNPs. Risk factors for clustering were identified with multivariable analysis and then Bayesian models and TransPhylo were used to infer the timing of transmission within clusters. Of the 2277 culture-positive patients, 70.1% (1596/2277) were migrants: 72.1% (1043/1446) of the migrants patients developed TB within two years of arriving in Longhua; 38.8% within 6 months of arriving; and 12.3% (104/843) had TB symptoms when they arrived. Only 15.4% of Longhua strains were in genomic clusters. More than one third (33.6%) of patients were not treated in Shenzhen but were involved in nearly one third of the recent transmission events. Clustering was associated with migrants not treated in Shenzhen, males, and teachers/trainers. TB in Longhua is prinicipally due to reactivation of infections in migrants, but a proportion may have had clinical or incipient TB upon arrival in the district. Patients diagnosed but not treated in Longhua were involved in recent local TB transmission. Controlling TB in Shenzhen will require strategies to comprehensively diagnose and treat active TB in the internal migrant population.

pH-Activatable Charge-Reversal Polymer-Based Nanocarriers for Targeted Delivery of Antihepatoma Compound.

Chemotherapy is one of the available cancer treatments which has been successfully employed to prolong the survival of cancer patients. However, it remains a major challenge to develop effective chemotherapeutic agents by reducing off-target toxicity, improving bioavailability, and effectively prolonging blood circulation. The pH profile of tumor cells is abnormal to that of normal cells, making it a potential breakthrough for designing effective chemotherapeutic drug agents. Here, the pH-activatable charge-reversal supramolecular nanocarriers, named MI7-ß-CD/SA NPs, were prepared through a simple and "green" constructive process. MI7-ß-CD/SA NPs possess both pH-induced charge-reversal and disassembly properties that were exploited to investigate the loading, delivery, and pH-responsive controlled release of the antitumor compound celastrol (CSL). CSL@MI7-ß-CD/SA NPs displayed low hemolysis, good biocompatibility, and targeted uptake. Furthermore, CSL@MI7-ß-CD/SA NPs exhibited superior apoptosis rates against SMMC-7721 cell lines compared with CSL, when CSL@MI7-ß-CD/SA NPs and CSL were administered at a mass concentration of 5.0 µg/mL, i.e., the CSL content in CSL@MI7-ß-CD/SA NPs was relatively lower than that of intact CSL. We expected that MI7-ß-CD/SA NPs featuring pH-triggered charge reversal could offer a promising controlled release strategy that would then facilitate the clinical conversion of antitumor drugs.

Sucrose-tannin-nanosilica hybrid bio-adhesive based on dual dynamic Schiff base and disulfide bonds with enhanced toughness and cohesion.

Herein, a high-performance sucrose-tannin bio-based adhesive is developed based on consisting of oxidized sucrose (OS), tannin acid (TA), SiO2 nanoparticles and 2,2'-disulfanediylbis (ethan-1-amine) (DBA) by a facile chemical cross-linking strategy. The OS-TA and OS-TA@SiO2 bio-based adhesives are characterized by XPS, FTIR, and 13C NMR, while the bonding performance is also investigated using shear strength test. Results show that the optimal formulation of OS-TA bio-based adhesive is a 2:1:1 mass ratio for OS: TA: DBA. When the mass fraction of SiO2 is 15 % and the solid content of main components is 50 %, the OS-TA@SiO2 bio-based adhesive has excellent bonding strength. Relative to OS-TA, the wet bonding strength of the OS-TA@SiO2 enhanced from 1.16 MPa to 1.85 MPa, while the dry bonding strength improved from 1.90 MPa to 2.50 MPa. The wood failure rate of the plywood fabricated by using the OS-TA@SiO2 bio-based adhesive reaches 80 %. Therefore, relying on the high flexibility of dynamic disulfide bonds, adding SiO2 nanoparticles into the adhesive system can facilitate greatly the mechanical interlocking effect and make the chemical cross-linking network more compact through the synergistic chemical interactions. This work provides new insights into producing green and renewable bio-based wood adhesives using sucrose and tannin.

Differences in clinical characteristics and liver injury between patients diagnosed with the Omicron subvariant BA.5.2 and the prototype of SARS-CoV-2: a single center retrospective study.

BACKGROUND: The purpose of this study was to investigate the differences between the clinical characteristics and the factors influencing liver injury in patients with the Omicron subvariant BA.5.2 (Omicron BA.5.2) and the prototype of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Between December 30, 2019 and November 30, 2022, 157 patients infected with the SARS-CoV-2 prototype and 199 patients infected with the Omicron BA.5.2 were included in this case-control, single-center, retrospective study. Differences in clinical characteristics and liver injury between the Omicron BA.5.2 patients and the prototype patients were subsequently analyzed. RESULTS: None of the Omicron BA.5.2 patients reached the critical state, and showed relatively milder symptoms including fever, cough, headache, muscle soreness, nausea or vomiting, diarrhea, anorexia and hypoxia. The Omicron BA.5.2 had a lower effect on body temperature (T), white blood cell (WBC) count, hematocrit (HCT), C-reactive protein (CRP) level, D-dimer, finger pulse oxygen saturation (SpO2) and lung lesions. The differences in liver injury between the two groups were related to the severity of the disease, T, blood oxygen levels, albumin (ALB), CRP, and medication usage. Gender, body mass index, and CRP levels influenced liver damage in the Omicron BA.5.2 patients. In particular, CRP was an independent risk factor for liver injury. Because the severity of liver function damage was considerably low, only a small number of Omicron BA.5.2 patients required liver-protective treatment. CONCLUSION: Liver injury is expected in the COVID-19 patients. The Omicron BA.5.2 patients showed milder symptoms of liver injury than the prototype patients. However, dynamic monitoring of liver function is warranted, especially for individuals presenting with elevated levels of CRP.

Effect of hydrogen/oxygen therapy for ordinary COVID-19 patients: a propensity-score matched case-control study.

BACKGROUND: Hydrogen/oxygen therapy contribute to ameliorate dyspnea and disease progression in patients with respiratory diseases. Therefore, we hypothesized that hydrogen/oxygen therapy for ordinary coronavirus disease 2019 (COVID-19) patients might reduce the length of hospitalization and increase hospital discharge rates. METHODS: This retrospective, propensity-score matched (PSM) case-control study included 180 patients hospitalized with COVID-19 from 3 centers. After assigned in 1:2 ratios by PSM, 33 patients received hydrogen/oxygen therapy and 55 patients received oxygen therapy included in this study. Primary endpoint was the length of hospitalization. Secondary endpoints were hospital discharge rates and oxygen saturation (SpO2). Vital signs and respiratory symptoms were also observed. RESULTS: Findings confirmed a significantly lower median length of hospitalization (HR = 1.91; 95% CIs, 1.25-2.92; p < 0.05) in the hydrogen/oxygen group (12 days; 95% CI, 9-15) versus the oxygen group (13 days; 95% CI, 11-20). The higher hospital discharge rates were observed in the hydrogen/oxygen group at 21 days (93.9% vs. 74.5%; p < 0.05) and 28 days (97.0% vs. 85.5%; p < 0.05) compared with the oxygen group, except for 14 days (69.7% vs. 56.4%). After 5-day therapy, patients in hydrogen/oxygen group exhibited a higher level of SpO2 compared with that in the oxygen group (98.5%±0.56% vs. 97.8%±1.0%; p < 0.001). In subgroup analysis of patients received hydrogen/oxygen, patients aged < 55 years (p = 0.028) and without comorbidities (p = 0.002) exhibited a shorter hospitalization (median 10 days). CONCLUSION: This study indicated that hydrogen/oxygen might be a useful therapeutic medical gas to enhance SpO2 and shorten length of hospitalization in patients with ordinary COVID-19. Younger patients or those without comorbidities are likely to benefit more from hydrogen/oxygen therapy.

Ureido Hyperbranched Polymer Modified Urea-Formaldehyde Resin as High-Performance Particleboard Adhesive.

The performance of urea-formaldehyde (UF) resin and its formaldehyde emission is a natural contradiction. High molar ratio UF resin performance is very good, but its formaldehyde release is high; low molar ratio UF resin formaldehyde release is reduced, but the resin itself performance becomes very bad. In order to solve this traditional problem, an excellent strategy of UF resin modified by hyperbranched polyurea is proposed. In this work, hyperbranched polyurea (UPA6N) is first synthesized by a simple method without any solvent. UPA6N is then added into industrial UF resin in different proportions as additives to manufacture particleboard and test its related properties. UF resin with a low molar ratio has a crystalline lamellar structure, and UF-UPA6N resin has an amorphous structure and rough surface. The results show that internal bonding strength increased by 58.5%, modulus of rupture increased by 24.4%, 24 h thickness swelling rate (%) decreased by 54.4%, and formaldehyde emission decreased by 34.6% compared with the unmodified UF particleboard. This may be ascribed to the polycondensation between UF and UPA6N, while UF-UPA6N resin forms more dense three-dimensional network structures. Finally, the application of UF-UPA6N resin adhesives to bond particleboard significantly improves the adhesive strength and water resistance and reduces formaldehyde emission, suggesting that the adhesive can be used as a green and eco-friendly adhesive resource for the wood industry.

CTHRC1, a novel gene with multiple functions in physiology, disease and solid tumors (Review).

Collagen triple helix repeat containing 1 (CTHRC1) is a gene discovered in 2005; it is highly conserved, and no homologous proteins have been disclosed thus far. A number of studies have shown that CTHRC1 is present in normal tissues and organs, and it has vital functions in physiological processes, including participating in the regulation of metabolism, arterial remodeling, bone formation and myelination of the peripheral nervous system. It has been reported that abnormal expression of CTHRC1 is involved in the carcinogenesis of various human organs, such as the breast, colon, pancreas, lung, stomach and liver. Therefore, the present review aims to collate all known findings and results on the regulation of CTHRC1 expression and related signaling pathways. To conclude, this review also provides a hypothesis of the functional mechanism of this gene.

Computed tomography enteroclysis combined with double-balloon endoscopy is beneficial to the diagnosis of small bowel submucosal tumors.

AIM: To compare the effectiveness and diagnostic accuracy of computed tomography enteroclysis (CTE), double-balloon endoscopy (DBE), and CTE with DBE (CTE/DBE) for detecting submucosal tumors (SMTs) in the small intestine. METHODS: The clinical data of 42 patients with pathologically confirmed small bowel SMTs seen at Renmin Hospital of Wuhan University between March 2012 and October 2020 were retrospectively analyzed. The value of CTE and DBE for detecting small bowel SMTs was then compared. RESULTS: No remarkable difference was found with regard to the sensitivity, positive and negative predictive values, as well as diagnostic accuracy rate between DBE and CTE, but the specificity of CTE was significantly higher than that of DBE (50.0% versus 25.0%, P = 0.001). Additionally, CTE/DBE also presented a higher sensitivity than CTE (97.4% versus 84.2%, P = 0.031). However, CTE/DBE and CTE were not greatly different in the positive predictive values and diagnostic accuracy rates. CONCLUSION: These findings suggest that CTE was better at detecting small bowel SMTs than DBE. Additionally, the combination of CTE and DBE is more beneficial for detecting SMTs in the small intestine.

Influence of AFP on surgical outcomes in non-B non-C patients with curative resection for hepatocellular carcinoma.

To study the clinical and prognostic features of non-B non-C alpha-fetoprotein (AFP)(-)-hepatocellular carcinoma (HCC) (NBNC-AFP(-)-HCC) and the relationship between the prognostic features of HCC and hepatitis B virus surface antigen (HBsAg) status and AFP. We enrolled 227 patients who underwent hepatic resection for HCC between January 1998 and December 2007 at Sun Yat-sen University Cancer Center, all of whom were diagnosed with HCC by pathology. All patients were stratified into one of four groups (B-AFP(+)-HCC, B-AFP(-)-HCC, NBNC-AFP(+)-HCC, and NBNC-AFP(-)-HCC) according to AFP levels and HBsAg status. The clinicopathologic and survival characteristics of NBNC-AFP(-)-HCC patients were compared with those of all other three groups. Out of the 105 NBNC-HCC patients, 43 patients (40.9%) had AFP-negative HCC. There were some differences in factors between the B-AFP(+) and NBNC-AFP(-) patients, such as age, body mass index (BMI), diabetes, and ALT (P < 0.05). On univariate analysis, tumour size, secondary tumour, and portal invasion were prognostic factors for overall survival (OS) and disease-free survival (DFS) (P < 0.05). Cox multivariate regression analysis suggested that tumour size and tumour number (P < 0.05) were independent predictors. In addition, compared with the B-AFP(+)-HCC, B-AFP(-)-HCC, and NBNC-AFP(+)-HCC groups, the NBNC-AFP(-)-HCC patients had the best DFS (P < 0.05). Compared with the B-AFP(+)-HCC and NBNC-AFP(+)-HCC groups, the NBNC-AFP(-)-HCC patients had better OS (P < 0.05), and survival rates were similar to those of B-AFP(-)-HCC patients. NBNC-AFP(-)-HCC patients had a relatively favourable prognosis. It can serve as a useful marker in predicting the risk of tumour recurrence in the early stages.

A meta-analysis of the diagnostic utility of biomarkers in cerebrospinal fluid in Parkinson's disease.

Biomarkers play important roles in the diagnosis and differential diagnosis of Parkinson's disease (PD). Thus, we carried out a systematic review and meta-analysis evaluating the diagnostic utility of cerebrospinal fluid (CSF) biomarkers to distinguish PD from atypical parkinsonian syndromes (APSs) and controls. Data for PD and APS and controls were extracted from 123 studies that reported the concentration of CSF biomarkers. Comparisons were presented using pooled Hedges' g. Sources of heterogeneity were evaluated using meta-regression, and subgroup and sensitivity analyses. We found that compared with controls, PD patients had lower levels of amyloid beta 1-42, phosphorylated tau, total tau, total α-synuclein, Zn, DJ-1, and YKL-40, and higher levels of oligomeric and phosphorylated α-synuclein. Moreover, lower CSF levels of neurofilament light chain, t-tau, YKL-40, and C-reactive protein were found in PD patients compared to those with multiple system atrophy. PD patients also had lower levels of NFL and higher levels of Aß42 compared with patients with progressive supranuclear palsy. Reduced levels of p-tau and t-tau and higher Aß42 levels were found in PD patients compared with patients with dementia with Lewy bodies. Finally, reduced NFL levels were found in patients with PD compared with patients with cortical basal degeneration. Therefore, we believe that the combinations of t-α-syn, Aß42, and NFL could be promising biomarkers for the differential diagnosis of PD and APSs.

Non-Coding RNAs of Extracellular Vesicles: Key Players in Organ-Specific Metastasis and Clinical Implications.

Extracellular vesicles (EVs) are heterogeneous membrane-encapsulated vesicles released by most cells. They act as multifunctional regulators of intercellular communication by delivering bioactive molecules, including non-coding RNAs (ncRNAs). Metastasis is a major cause of cancer-related death. Most cancer cells disseminate and colonize a specific target organ via EVs, a process known as "organ-specific metastasis". Mounting evidence has shown that EVs are enriched with ncRNAs, and various EV-ncRNAs derived from tumor cells influence organ-specific metastasis via different mechanisms. Due to the tissue-specific expression of EV-ncRNAs, they could be used as potential biomarkers and therapeutic targets for the treatment of tumor metastasis in various types of cancer. In this review, we have discussed the underlying mechanisms of EV-delivered ncRNAs in the most common organ-specific metastases of liver, bone, lung, brain, and lymph nodes. Moreover, we summarize the potential clinical applications of EV-ncRNAs in organ-specific metastasis to fill the gap between benches and bedsides.

Evaluating the ability of the NLHA2 and artificial neural network models to predict COVID-19 severity, and comparing them with the four existing scoring systems.

To improve the identification and subsequent intervention of COVID-19 patients at risk for ICU admission, we constructed COVID-19 severity prediction models using logistic regression and artificial neural network (ANN) analysis and compared them with the four existing scoring systems (PSI, CURB-65, SMARTCOP, and MuLBSTA). In this prospective multi-center study, 296 patients with COVID-19 pneumonia were enrolled and split into the General-Ward-Care group (N = 238) and the ICU-Admission group (N = 58). The PSI model (AUC = 0.861) had the best results among the existing four scoring systems, followed by SMARTCOP (AUC = 0.770), motified-MuLBSTA (AUC = 0.761), and CURB-65 (AUC = 0.712). Data from 197 patients (training set) were analyzed for modeling. The beta coefficients from logistic regression were used to develop a severity prediction model and risk score calculator. The final model (NLHA2) included five covariates (consumes alcohol, neutrophil count, lymphocyte count, hemoglobin, and AKP). The NLHA2 model (training: AUC = 0.959; testing: AUC = 0.857) had similar results to the PSI model, but with fewer variable items. ANN analysis was used to build another complex model, which had higher accuracy (training: AUC = 1.000; testing: AUC = 0.907). Discrimination and calibration were further verified through bootstrapping (2000 replicates), Hosmer-Lemeshow goodness of fit testing, and Brier score calculation. In conclusion, the PSI model is the best existing system for predicting ICU admission among COVID-19 patients, while two newly-designed models (NLHA2 and ANN) performed better than PSI, and will provide a new approach for the development of prognostic evaluation system in a novel respiratory viral epidemic.